Lipidbinding

Lipid binding refers to non-covalent interactions between a molecule, most commonly a protein or peptide, and lipids, typically within cellular membranes or lipid aggregates. Lipid binding is central to membrane targeting, signaling, and lipid metabolism, and can involve proteins binding to phospholipids, sterols, or specialized lipid species such as phosphoinositides.

Binding arises through several mechanisms. Electrostatic attraction between positively charged amino acids and negatively charged lipid headgroups (for example phosphatidylserine or phosphoinositides) guides association with membranes. Hydrophobic interactions or shallow insertion of amphipathic helices can anchor proteins at the bilayer. Some interactions require divalent cations such as calcium.

Many proteins contain lipid-binding domains that confer specificity for particular lipids. Examples include pleckstrin homology (PH) domains that recognize phosphoinositides, C2 domains that bind phospholipids in a calcium-dependent manner, PX domains for PI3P, ENTH and other BAR domain-containing modules, FYVE domains, and START domains.

Roles include targeting of cytosolic factors to membranes, regulation of signaling pathways, vesicular trafficking, and lipid transport and metabolism. Lipid binding can regulate enzyme activity, recruit adaptor proteins, or induce membrane curvature and fission.

Experimental approaches to study lipid binding include lipid-overlay assays and liposome binding or co-sedimentation assays, surface plasmon resonance and isothermal titration calorimetry, and fluorescence-based methods. Structural and biophysical methods such as X-ray crystallography, NMR, cryo-electron microscopy, and computational modeling provide mechanistic insight.

Dysregulation of lipid–protein interactions is associated with diseases including cancer, neurodegeneration, and metabolic disorders. Understanding lipid binding informs basic biology and can guide the development of therapeutics that modulate membrane association or lipid recognition.